Cytokeratin 17 and Ki-67: Immunohistochemical markers for the differential diagnosis of keratoacanthoma and squamous cell carcinoma.

The clinical and histopathological distinction between keratoacanthoma (KA) and squamous cell carcinoma (SCC) is essential, but frequently difficult to make. The utility of CK17 and Ki-67 expression in distinguishing between KA and SCC was investigated. Immunohistochemical staining patterns for CK17 and Ki-67 were evaluated in 24 KA and 27 SCC cases. The pattern of staining was evaluated as central, peripheral or diffuse, according to the basal/peripheral and suprabasal/central cell staining of tumor lobules. The sensitivity and specificity of the central CK17 staining pattern in the identification of KA were 92 and 70%, respectively. Additionally, the sensitivity and specificity of the diffuse Ki-67 staining pattern in the identification of SCC were 81 and 100%, respectively. The results of the present study suggest that a diffuse Ki-67 staining pattern may be used to diagnose SCC, while a central CK17 staining pattern indicates KA. However, the KA-like SCC cases exhibited mixed patterns, which limits the effectiveness of these markers.

Intralymphatic nevus cells in benign nevi.

The histogenesis of nevus cell aggregates in lymph nodes lesion is controversial, and various hypotheses have been used to explain their origin. One of them is the transport of cells from cutaneous nevi or lesions to lymph nodes, called mechanical transport theory. We investigated in our cases of benign nevi to obtain evidence to substantiate this theory. A total of 369 benign cutaneous nevi were prospectively evaluated in excisional biopsy samples. Immunohistochemical stainings for CD31 and podoplanin (D2-40) were performed in the cases with intralymphatic nevus cell aggregate (ILNA), suspected for ILNA, and/or intralymphatic nevus cell protrusion. A total of 13 ILNAs were found in 10 patients. Six ILNA were verified with their histology as well as immunohistochemically with D2-40 and CD31. Protrusions of nevus cells inside the lymphatics (intralymphatic nevus cell protrusion) were seen in all cases of ILNA and also in 27 nevi where an ILNA was not observed. In most nevi, the perilymphatic orientation of nevus cells and their affinity to the lymphatics were observed. We suggested that ILNAs can be dislodged with local minor trauma and be carried inside the lymphatic vessel to the draining lymph node. Besides, whether ILNA or not, nevus cells could also move toward lymphatic spaces with mechanical effects due to their affinity to lymphatics and their localizations that are very close to the endothelium. Our findings might support the mechanical transport theory.

Malignant Phyllodes Tumor Including Aneurysmal Bone Cyst-Like Areas in Pregnancy - a Case Report and Review of the Literature.

BACKGROUND: Malignant phyllodes tumors of the breast are rare biphasic neoplasms. Only few cases related to pregnancy have been reported. CASE REPORT: A 37-year-old woman presented with swelling and pain in her left breast as well as hyperemia on the breast skin, 4 weeks after labor. In her family history, her aunt and maternal cousin had had a breast cancer diagnosis. Clinical evaluation of the patient was consistent with a breast abscess. Therefore, abscess drainage and biopsy from the cavity wall were performed. However, the biopsy was diagnosed as malignant phyllodes tumor. An evaluation by ultrasonography showed a well-defined hypoechoic mass with many cystic spaces covering the entire breast tissue. Therefore, a simple mastectomy was performed. Microscopic examination revealed a high-grade malignant phyllodes tumor. Additionally, bone cyst-like areas in the form of sponge-like blood-filled non-endothelialized spaces were observed. CONCLUSIONS: Since the breasts become larger due to the physiological changes during pregnancy, any underlying breast lesions may be obscured. Therefore, clinical breast examination in the first visit of pregnancy is important.

Benign mixed tumour of the breast and breast skin, two cases with diagnostic difficulties.

We present two cases of pleomorphic adenoma, one that developed in the breast parenchyma and the other in the breast skin, with their histopathological differential diagnosis.

Nodule-Forming Pseudoangiomatous Stromal Hyperplasia of the Breast: Report of Three Cases.

Pseudoangiomatous stromal hyperplasia (PASH) is a benign proliferative entity of mammary stroma. It is generally found as an incidental finding. It may rarely present as a palpable nodule. Three patients, who were 29, 45, and 58 years of age, were referred to our clinic with nodule and pain in the breast. The physical examinations and ultrasound findings of all three patients were consistent with fibroadenoma. Core biopsies were performed and reported as "benign breast parenchyma including stromal fibrosis." PASH areas were noted in one case. The excision specimens were observed as solid nodular masses with smooth external surfaces and white in colour. Microscopically, well-demarcated hyalinized stroma, including slit-like pseudovascular spaces lined by bland spindle cells, was observed. Immunohistochemically, these cells showed positive staining for CD34 and negative staining for CD31. Nodule-forming PASH mostly confuses with fibroadenoma with respect to clinical examination and radiological findings. Definite diagnosis requires histopathological verification. Differential diagnosis should be made with low grade angiosarcoma, fibroepithelial tumors, and myofibroblastoma.

Matrix-Producing Carcinoma of the Breast: Case Report.

Matrix-producing carcinoma (MPC) is an uncommon variant of metaplastic carcinoma. It was first described by Wargotz and Norris in 1989 as invasive breast carcinoma with direct transition to cartilaginous stroma without intervening spindle cell component. Since then, several studies, mostly in the form of case reports or case series, have been reported and the origin of tumor cell, importance of appropriate terminology for the tumor, histopathological differential diagnosis, benign breast lesions that the tumor could correlate with, and prognosis and consequently the treatment modalities have been discussed. A 43-year-old woman referred to our clinic with a lump in her left breast. Physical examination and radiological findings were consistent with malignancy. Core biopsy of the lesion was reported as "invasive breast carcinoma" and then breast-conserving surgery with sentinel lymph node dissection were performed. The case was diagnosed as MPC of the breast. The literature findings imply epithelial cell (ductal and/or myoepithelial) nature of this tumor. The prognosis is still controversial. Histopathological evaluation of sufficiently sampled surgical excision material is important to recognize and make a correct diagnosis.

The relationship between adrenal gland morphometric changes and postmortem interval in rats: a stereological study.

The importance of determining time of death is crucial to forensic cases. The ability to use adrenal gland volume changes and adrenal medulla chromaffin cell counts to obtain the postmortem interval was examined in this study. A total of 15 rats were sacrificed by cervical dislocation and divided into three groups. The left adrenal glands were quickly excised in the first group at 0 h, in the second group at 12 h and in the third group at 24 h. Subsequently, the samples were fixed in 10% formalin solution and embedded in paraffin according to standard procedures. Ten to fifteen sections were obtained from each left adrenal gland by taking 30 µm thick sections; then, the sections were stained with hematoxylin-eosin (HE). The adrenal cortex and medullar volumes were calculated by Cavalieri's principle, which is a stereological method. The adrenal medullary chromaffin cell count was evaluated by the optical fractionator method. The total volume of the adrenal gland was determined as 4.82±1 mm(3) at 0 h, 6.32±0.28 mm(3) at 12 h and 8.35±1.73 mm(3) at 24 h. Increases in the adrenal cortex, adrenal medulla and the total volume of the adrenal gland at 12 and 24 h postmortem compared with at 0 h were statistically significant (p<0.05). The difference between the groups in terms of the total number chromaffin cells was statistically significant (p<0.05). In this preliminary study, we evaluated the total volume of the adrenal gland and the number of chromaffin cells of the adrenal medulla. We concluded that these parameters could be used reliably in determining the postmortem interval.

Occult axillary lymph node metastases do not have prognostic significance in early stage breast cancer.

BACKGROUND: Axillary lymph node status is one of the most powerful prognostic indicators in patients with breast cancer and has implications for adjuvant treatment. It has been demonstrated that enhanced histologic evaluation of axillary lymph nodes, including serial sectioning of paraffin tissue blocks and immunohistochemical (IHC) staining, increases the rate of detection of occult metastases. The clinical significance of occult lymph node metastases has been the subject of debate. METHODS: In the current study, the authors identified 267 patients who underwent axillary lymph node dissection (ALND) between 1987 and 1995 and were lymph node negative according to a routine pathologic evaluation, which included the complete submission of all lymph nodes and an examination of 1 hematoxylin and eosin (H&E)-stained section per paraffin block. Patients did not receive systemic chemotherapy or hormone therapy. All of the dissected lymph nodes from these patients were re-evaluated by intensified pathologic methods (serial sectioning with H&E levels plus IHC). Occult metastases were categorized by detection method and size. The clinical significance of the occult metastases was determined. RESULTS: Thirty-nine patients (15%) who had lymph node-negative results on routine evaluation of their ALND specimens had occult metastases identified. Eight of these patients (20%) had macrometastases >2.0 mm, 15 (40%) had micrometastases (range, >0.2 mm to ≤2 mm), and 16 (40%) had isolated tumor cells (≤0.2 mm). The presence of occult metastases and the size of metastases did not affect recurrence-free or overall survival. CONCLUSIONS: The presence of occult metastasis did not have clinical significance in this cohort of patients with early stage breast cancer.

Expression and amplification of Topoisomerase-2α in type 1 and type 2 papillary renal cell carcinomas and its correlation with HER2/neu amplification.

The current study was undertaken to investigate chromosomal and genetical aberrations leading to overexpression of Topoisomerase-2α (TOP2α) and to reveal the possible association of these aberrations with HER2/neu overexpression and gene amplification, and to search for the relationship between TOP2α and HER2/neu status with prognostical biomarkers in papillary renal cell carcinoma (RCC), a group of tumors with diverse molecular, chromosomal and clinical features. Archival cases of papillary RCC obtained from Departments of Pathology of Pamukkale, Ege and Dokuz Eylul Universities were studied in two groups (type 1 and type 2) each containing 20 cases. The level of TOP2α and HER2/neu expression by tumor cells were determined immunohistochemically. A multicolor FISH probe was used to define both amplification of HER2/neu and TOP2α genes, and polysomy 17. The ratio of cells expressing TOP2α in type 1 and type 2 papillary RCC were 24.29% and 6.89%, respectively. The difference was statistically significant comparing the average or median values of groups separately (p = 0.002). The expression levels of TOP2α and HER2/neu were also correlated. TOP2α and HER2/neu were co-amplified in both groups. Immunohistochemical expression was not observed in 15 of 23 cases with HER2/neu amplification. The most frequent finding detected by FISH method was polysomy of chromosome 17. We had contradictory results compared with the findings reported in the limited numbers of literature. It shows us that papillary RCC constitute a heterogenous group of tumors with various cytogenetic features and morphological classification of these tumors may not be compatible with their molecular characteristics.

Secondary involvement of the breast in T-cell non-Hodgkin lymphoma, an unusual example mimicking inflammatory breast carcinoma.

Non-Hodgkin lymphoma of the breast is a rare malignancy and present with almost equal frequency either as a primary or a secondary disease. Survival is poor in most cases of secondary breast lymphoma because of their advanced stage. We report a 35-year-old woman presenting with dyspnea as well as swelling, tenderness, and ruddiness in the left breast with non-cyclic pain for several months and maculopapular skin eruption in the same breast. Physical examination revealed fixed lymphadenopathies in both axillary regions. Radiologic evaluations (bilateral mammaograpy and ultrasonography) showed skin thickening in the left breast, asymmetrical densities in both breasts, and confirmed lymphadenopathies in the axillary regions. Excisional biopsies were performed to the left axillary lymph nodes and the breast skin eruptions. The histologic and immunohistochemical features were diagnosed as an ALK (-) anaplastic large cell lymphoma. A Computed Tomography examination was performed for staging the lymphoma and then chemotherapy was started. Thirty months after the diagnosis, the patient is still alive with disease. Because of the presence of systemic symptoms such as skin involvement and generalized lymphadenopathies (mediastinal, axillary or cervical), T cell lymphoma cases with breast involvement could mimic the clinical presentation of inflammatory breast carcinoma. Pathologic examination is needed for the correct diagnosis.

Primary neuroendocrine carcinoma of the breast: a case report.

Primary neuroendocrine carcinoma of the breast is an extremely rare tumor. We present our experience of primary neuroendocrine carcinoma of the breast in a 76-year-old woman. Surgical biopsies from breast and axillary lymphadenopathy showed a neuroendocrine carcinoma. Immunohistochemical staining of tumor cells with GCDFP15, NSE and chromogranin were positive. Computed tomography scans of the chest and abdomen showed no lesion for metastasis or another primary origin. Adjuvant hormone therapy was given, since the tumor was immunohistochemically receptor positive.

Insertion/deletion polymorphism of the angiotensin I-converting enzyme gene in patients with breast cancer and effects on prognostic factors.

The aims of the present study were to investigate the distribution of the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene in breast cancer patients and the association between ACE genotypes and clinicopathologic features, as well as their effects on prognosis. We assessed the I/D polymophism of the ACE gene by using polymerase chain reaction from peripheral blood in breast cancer and healthy age-matched women. The clinicopathologic parameters of breast cancer patients were obtained from medical records. Of the 57 patients, 31 (54.4%) had DD, 24 (42.1%) had ID, and 2 (3.5%) had II genotypes. In control subjects, 33 (63.5%) had DD, 12 (23.1%) had ID, and 7 (13.4%) had II genotypes. The ID genotype was seen more commonly in breast cancer patients (p = .03). When the combination of ID and II genotypes was used as a reference group, the DD genotype was associated with negative hormone receptor status (p = .003), tumor size (p = .054), and lymph node involvement (p = .07) but not histologic high grade and c-erb B2 overexpression. These results suggest that the DD genotype may accompany poor prognostic factors and influence the tumor course.

Primary peritoneal serous psammocarcinoma with recurrent disease and metastasis: a case report and review of the literature.

BACKGROUND: Psammocarcinoma is a rare variant of serous carcinoma arising from either ovary or peritoneum. Although behavior of tumor is uncertain, it has been suggested to be similar to serous carcinomas of low malignant potential. CASE: A 67-year-old woman was admitted with an abnormal vaginal bleeding and abdomino-pelvic pain. Computed tomography showed a heavily calcified rectovaginal mass that was histologically characterized by numerous psammoma bodies and low-grade cytological features. Following the primary surgery, the patient received 9 cycles of chemotherapy. Five years later, she presented with diffuse recurrence and 1 year later, with metastasis to the vertebra. CONCLUSION: Although psammocarcinoma is known to behave in a more indolent course, clinicians should be aware that patients with this disease may have a clinically aggressive, recurrent, and metastatic tumor that necessitated systemic therapy.

Ectopic pancreas of the gastric antrum contiguous to a gastrointestinal stromal tumor manifesting as upper gastrointestinal bleeding: report of a case.

A 54-year-old woman was referred to us for investigation of recurrent episodes of melena. Gastroduodenal endoscopic examination revealed a hemorrhagic, polypoid tumor, about 3 cm in diameter, in the posterior wall of the gastric antrum, near the greater curvature. The lesion had a smooth surface with ulceration, and was fixed to the sublying planes. The source of the bleeding was the mucosa overlying the tumor. We performed a distal subtotal gastrectomy with Roux-en-Y anastomosis. Histopathological examination of the resected specimen revealed an ectopic pancreas and a gastrointestinal stromal tumor contiguous to the ectopic pancreatic tissue in the gastric antrum. The patient was discharged after an uneventful postoperative course and has not experienced any recurrence of symptoms since.

Association between the polymorphism of the angiotensin-converting enzyme gene and tumor size of breast cancer in premenopausal patients.

The association between the polymorphism of the angiotensin-converting enzyme (ACE) gene and breast cancer risk has been extensively studied, however, the studies about the prognostic factors and ACE gene polymorphism are limited in number. Our aims were to analyze the distribution of the insertion/deletion (I/D) polymorphism of the ACE gene in Turkish premenopausal patients with breast cancer, which is more aggressive than the postmenopausal counterpart, and to assess whether DD genotype is associated with poor prognostic factors. The DD genotype has been shown to be associated with the increased serum and tissue levels of ACE, compared to those in II and ID genotypes. ACE genotypes were determined by polymerase chain reaction in 44 Turkish premenopausal patients with breast cancer and in 46 age-matched healthy premenopausal women. ACE genotypes are distributed in patients and control subjects as follows; DD is present in 25 (56.8%), ID in 17 (38.6%), and II in 2 (4.5%) patients, and DD in 28 (60.9%), ID in 12 (26.1%), and II in 6 (13.0%) healthy subjects, respectively. D and I alleles were found in 76.1% and 23.9% of the patients, while 73.9% and 26.1% in healthy subjects, respectively. In breast cancer patients, no significant association was observed between the ACE genotypes and poor prognostic factors, such as negative hormone receptor status, histological grade, lymph node involvement, higher number of lymph node metastases, and c-erb B2 overexpression, except that tumor size greater than 2 cm is associated with DD genotype (p = 0.02). Thus, ACE may influence the local tumor growth of breast cancer in premenopausal patients.